Synthesis, Structure, and Activity of Supramolecular Mimics for the Active Site and Arg141 Residue of Copper, Zinc−Superoxide Dismutase

Two supramolecular complexes, [Cu(L)(H2O)2(β-CD)](ClO4)2·10.5H2O·CH3OH (1) and [Cu(L)(H2O)2(β-GCD)](HClO4)(ClO4)2·10H2O (2) (L = 4-(4‘-tert-butyl-benzyl)diethylenetriamine, β-CD = β-cyclodextrin, and β-GCD = mono-6-deoxy-6-guanidinocycloheptaamylose cation), have been synthesized. The structure of 1 has been characterized
by X-ray crystallography. The 4-tert-butyl-benzyl of [Cu(L)(H2O)2]2+ moiety in 1 as a guest inserts into the hydrophobic
cavity of the β-CD as a host along the primary hydroxyl side. On the basis of the structure data of 1, complex 2
was modeled, which showed that the distance between the Cu and C atom of the guanidinium is 5.2 Å, comparable
to the corresponding distance in bovine erythrocyte Cu, Zn−SOD (5.9 Å) (SOD = superoxide dismutase). Apparent
inclusion stability constants of the host and the guest were measured to be 0.66 (±0.01) × 104 and 1.15 (±0.03)
× 104 M-1 for 1 and 2 respectively. The electronic absorption bands and electronic reflection bands of each complex
are almost the same, indicating an identical structure of the complex in aqueous solution and in solid state. The
two complexes showed quasi-reversible one-electron Cu(II)/Cu(I) redox waves with redox potentials of −0.345 and
−0.338 V for 1 and 2, respectively. Their SOD-like activities (IC50) were measured to be 0.30 ± 0.01 and 0.17 ±
0.01 μM by xanthine/xanthine oxidase-NBT assay. The enhanced SOD activity of 2 by ∼40% compared with 1
suggests that the guanidyl cation in the host of the supramolecular system of 2 can effectively mimic the side chain
of Arg141 in the enzyme, which is known to be essential for high SOD activity possibly through steering of the
superoxide substrate to and from the active copper ion.